Medical device inserters and processes of inserting and using medical devices

ABSTRACT

An apparatus for insertion of a medical device in the skin of a subject is provided, as well as methods of inserting medical devices.

RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 13/071,487 filed Mar. 24, 2011 entitled “Medical DeviceInserters and Processes of Inserting and Using Medical Devices,” whichclaims the benefit of U.S. Provisional Application Nos. 61/317,243,filed Mar. 24, 2010; 61/345,562, filed May 17, 2010; 61/361,374, filedJul. 2, 2010; 61/411,262, filed Nov. 8, 2010, the disclosures of whichare incorporated herein by reference for all purposes.

INCORPORATION BY REFERENCE

Patents, applications and/or publications described herein, includingthe following patents, applications and/or publications are incorporatedherein by reference for all purposes: U.S. Pat. Nos. 4,545,382;4,711,245; 5,262,035; 5,262,305; 5,264,104; 5,320,715; 5,356,786;5,509,410; 5,543,326; 5,593,852; 5,601,435; 5,628,890; 5,820,551;5,822,715; 5,899,855; 5,918,603; 6,071,391; 6,103,033; 6,120,676;6,121,009; 6,134,461; 6,143,164; 6,144,837; 6,161,095; 6,175,752;6,270,455; 6,284,478; 6,299,757; 6,338,790; 6,377,894; 6,461,496;6,503,381; 6,514,460; 6,514,718; 6,540,891; 6,560,471; 6,579,690;6,591,125; 6,592,745; 6,600,997; 6,605,200; 6,605,201; 6,616,819;6,618,934; 6,650,471; 6,654,625; 6,676,816; 6,730,200; 6,736,957;6,746,582; 6,749,740; 6,764,581; 6,773,671; 6,881,551; 6,893,545;6,932,892; 6,932,894; 6,942,518; 7,041,468; 7,167,818; and 7,299,082;7,381,184; 7,740,581; 7,811,231 U.S. Published Application Nos.2005/0182306; 2006/0091006; 2007/0056858; 2007/0068807; 2007/0095661;2007/0108048; 2007/0149873; 2007/0149875; 2007/0199818; 2007/0227911;2007/0233013; 2008/0058625; 2008/0064937; 2008/0066305; 2008/0071157;2008/0071158; 2008/0081977; 2008/0102441; 2008/0148873; 2008/0161666;2008/0179187; 2008/0267823; 2008/0319295; 2008/0319296; 2009/0018425;2009/0247857; 2009/0257911, 2009/0281406; 2009/0294277; 2009/0054748;2009/0054749; 2010/0030052; 2010/0065441; 2010/0081905; 2010/0081909;2010/0213057; 2010/0325868; 2010/0326842; 2010/0326843; 2010/0331643;2011/0046466; U.S. patent application Ser. Nos. 12/624,767; 12/625,185;12/625,208; 12/625,524; 12/625,525; 12/625,528; 12/628,177; 12/628,198;12/628,201; 12/628,203; 12/628,210; 12/698,124; 12/698,129; 12/699,653;12/699,844; 12/714,439; 12/730,193; 12/794,721; 12/807,278; 12/842,013;12/870,818; 12/871,901; 12/873,301; 12/873,302; 13/011,897; and U.S.Provisional Application Nos. 61/238,646; 61/246,825; 61/247,516;61/249,535; 61/317,243; 61/325,155; 61/345,562; and 61/359,265.

BACKGROUND OF THE INVENTION

The detection and/or monitoring of glucose levels or other analytes,such as lactate, oxygen, A1C, or the like, in certain individuals isvitally important to their health. For example, the monitoring ofglucose is particularly important to individuals with diabetes.Diabetics generally monitor glucose levels to determine if their glucoselevels are being maintained within a clinically safe range, and may alsouse this information to determine if and/or when insulin is needed toreduce glucose levels in their bodies or when additional glucose isneeded to raise the level of glucose in their bodies.

Growing clinical data demonstrates a strong correlation between thefrequency of glucose monitoring and glycemic control. Despite suchcorrelation, many individuals diagnosed with a diabetic condition do notmonitor their glucose levels as frequently as they should due to acombination of factors including convenience, testing discretion, painassociated with glucose testing, and cost.

Devices have been developed for the automatic monitoring of analyte(s),such as glucose, in bodily fluid such as in the blood stream or ininterstitial fluid (“ISF”), or other biological fluid. Some of theseanalyte measuring devices are configured so that at least a portion ofthe devices are positioned below a skin surface of a user, e.g., in ablood vessel or in the subcutaneous tissue of a user, so that themonitoring is accomplished in vivo.

With the continued development of analyte monitoring devices andsystems, there is a need for such analyte monitoring devices, systems,and methods, as well as for processes for manufacturing analytemonitoring devices and systems that are cost effective, convenient, andwith reduced pain, provide discreet monitoring to encourage frequentanalyte monitoring to improve glycemic control.

SUMMARY

An apparatus for inserting a medical device at least partially throughthe skin of a subject is provided, which includes a first subassemblyand a second subassembly. The first subassembly includes a sheathdefining a distal surface for placement on the skin of the subject, ahandle movable between a proximal position and distal position, a devicesupport for supporting the medical device and defining an aperturetherethrough, the device support coupled to the handle, a sharp supportfor supporting a sharp extending through said aperture and coupled tothe device support, and a first driver for biasing the sharp supporttowards the proximal position. The second subassembly includes a housingconfigured for removable attachment to the first subassembly, and asecond driver for advancing the sharp support towards the distalposition.

In some embodiments, the first subassembly and the second subassemblyare modular components. In some embodiments, the first subassembly iscapable of independent operation without the second subassembly. In someembodiments, the driver of the first subassembly is capable of operationby a user without the second subassembly. In some embodiments, thedriver of the first subassembly is actuable by depressing an actuationswitch or button. In some embodiments, the second subassembly isconfigured to actuate the actuation switch or button of the firstsubassembly.

In some embodiments, the second driver includes a rotatable cam or atorsion spring. In some embodiments, the second driver includes eitheran axial driver and a crank assembly or a compression spring. In someembodiments, the first driver includes a compression spring, or atorsion spring.

In some embodiments, the handle is at least partially disposedsurrounding the sheath. In some embodiments, a retention member forretaining the device support in the distal position is provided. Thedevice support may be coupled to the handle until the device supportreaches a distal position.

In some embodiments, the first subassembly is configured for a singleuse. In some embodiments, the second subassembly is configured formultiple uses.

Embodiments of analyte sensors are provided which include a body havinga proximal section and a distal section. The distal section may belongitudinally aligned with the proximal section. An intermediatesection may be included between the proximal and distal sections, and insome embodiments the intermediate section is laterally displaced from atleast the distal member.

In some embodiments, the proximal end is received within a needle seatto create an anchor region to allow the sensor body to slide into anopening defined in the insertion sharp but prevent the sensor body frominadvertently slipping out of the insertion needle. In some embodiments,a width of the distal section of the sensor body is sized to fit withinthe opening of the insertion sharp. In certain embodiments, the openingin the sharp has a diameter of about 20 gauge to about 26 gauge, e.g.,21 gauge to about 25 gauge, where in certain embodiments the sharp is 21gauge or 23 gauge or 25 gauge. Such sharp may be used with a sensorhaving a width or diameter —at least the portion that is carried by thesharp—of about 0.20 mm to about 0.80 mm, e.g., about 0.25 mm to about0.60 mm, where in some embodiments the width or diameter of at least aportion of a sensor is 0.27 mm or 0.33 mm or 0.58 mm.

In some embodiments, the intermediate member includes a plane-alteringportion. The plane-altering portion allows the proximal section of thesensor body to be in a plane different than the distal section of thesensor body. In some embodiments, the proximal section and the distalsection are in planes substantially perpendicular to each other, e.g.,the area may define an angle of about 120° to about 60°, e.g., about90°.

In certain embodiments, apparatuses for inserting a medical device atleast partially through the skin of a subject are provided which includea sheath defining a distal surface for placement on the skin of thesubject; a handle movable between a proximal position and distalposition; a device support for supporting the medical device anddefining an aperture therethrough, the device support coupled to thehandle; a sharp support for supporting a sharp extending through saidaperture and coupled to the device support; and driver for biasing thesharp support towards the proximal position.

In some embodiments, the driver includes a compression spring. In someembodiments, the handle is at least partially disposed surrounding thesheath. In some embodiments, a stop portion for retaining the devicesupport in the distal position is included. In some embodiments, thedevice support is coupled to the handle until the device support reachesa distal position. In some embodiments, the device support is uncoupledfrom the sharp support when the device support reaches the distalposition.

In some embodiments, a second assembly interfaces with the insertiondevices or first subassembly. The second assembly automates theinsertion segment motion of the described inserter. The second assemblymay include a housing configured for removable attachment to the firstsubassembly, a handle configured for longitudinal movement with respectto the housing, an actuator configured for longitudinal movement withrespect to the housing, a release member either located on the actuatoror handle which is actuated upon the handle reaching a predeterminedposition, a driver element coupled between the handle and the actuator,energized upon distal movement of the handle, which drives the actuatordistally once the release member is actuated, and a second driver whichis also energized upon distal movement of the handle, that applies aproximal force on the handle that returns the handle to a proximalposition after pressure is relieved from the handle post insertion. Thesecond driver, coupled through the handle, also provides a proximalforce to return the actuator to its proximal position where the releasemember is reengaged.

In some embodiments, the first driver includes a compression spring, ora torsion spring. In some embodiments, the handle is at least partiallydisposed surrounding the sheath. In some embodiments, a retention memberfor retaining the device support in the distal position is provided. Thedevice support may be coupled to the handle until the device supportreaches a distal position.

In some embodiments, the first subassembly is configured for a singleuse. In some embodiments, the first subassembly is configured formultiple uses. In some embodiments, the second subassembly is configuredfor multiple uses.

These and other features, objects, and advantages of the disclosedsubject matter will become apparent to those persons skilled in the artupon reading the detailed description as more fully described below.

BRIEF DESCRIPTION OF THE DRAWINGS

A detailed description of various aspects, features, and embodiments ofthe subject matter described herein is provided with reference to theaccompanying drawings, which are briefly described below. The drawingsare illustrative and are not necessarily drawn to scale, with somecomponents and features being exaggerated for clarity. The drawingsillustrate various aspects and features of the present subject matterand may illustrate one or more embodiment(s) or example(s) of thepresent subject matter in whole or in part.

FIG. 1 illustrates an analyte monitoring system for real time analyte(e.g., glucose) measurement, data acquisition and/or processing incertain embodiments;

FIGS. 2-3 are views of an electrochemical sensor in accordance with afurther embodiment of the disclosed subject matter;

FIGS. 4-5 are schematic views of a needle hub in accordance with oneembodiment of the disclosed subject matter;

FIG. 6 is a distal end view of a sharp in accordance with one embodimentof the disclosed subject matter;

FIG. 7 is a side view of a sharp in accordance with one embodiment ofthe disclosed subject matter;

FIG. 8 is a side view of a sharp in accordance with one embodiment ofthe disclosed subject matter;

FIG. 9 is a perspective view of a sharp in accordance with oneembodiment of the disclosed subject matter;

FIG. 10 is a schematic view of an alternate embodiment for forming asharp to be used in an inserter in accordance with one embodiment of thedisclosed subject matter;

FIG. 11 is a perspective view of an inserter in accordance with oneembodiment of the disclosed subject matter;

FIG. 12 is a perspective view with parts separated of an inserter inaccordance with one embodiment of the disclosed subject matter;

FIG. 13 is an enlarged sectional view with parts separated of aninserter in accordance with one embodiment of the disclosed subjectmatter;

FIG. 14 is a perspective view of another embodiment of an inserter inaccordance with the disclosed subject matter;

FIG. 15 is a side view of the inserter of FIG. 14 in accordance with thedisclosed subject matter;

FIGS. 16-17 are cross-sectional views of the inserter of FIG. 14 inaccordance with the disclosed subject matter;

FIGS. 18-19 are perspective views of an inserter in accordance withanother embodiment of the disclosed subject matter;

FIGS. 20-21 are perspective views of the inserter of the embodiment ofFIG. 18 in combination with the inserter of FIG. 14 in accordance withanother embodiment of the disclosed subject matter;

FIGS. 22-24 are side views of the inserter of the embodiment of FIG. 18in combination with the inserter of FIG. 14 in accordance with anotherembodiment of the disclosed subject matter;

FIGS. 25-26 are perspective views of an inserter in accordance withanother embodiment of the disclosed subject matter;

FIGS. 27-28 are perspective views of the inserter of the embodiment ofFIG. 25 in combination with the inserter of FIG. 14 in accordance withanother embodiment of the disclosed subject matter;

FIGS. 29-31 are side views of the inserter of the embodiment of FIG. 25in combination with the inserter of FIG. 14 in accordance with anotherembodiment of the disclosed subject matter;

FIG. 32 is a side view of an inserter in accordance with anotherembodiment of the disclosed subject matter;

FIG. 33 is a perspective view of an inserter in accordance with anotherembodiment of the disclosed subject matter;

FIGS. 34-43 are views of the inserter of FIGS. 32-33 showing theinserter actuation process;

FIG. 44 is a cross-sectional view of another inserter in accordance withthe disclosed subject matter;

FIG. 45 is an exploded perspective view of the inserter of FIG. 44 inaccordance with the disclosed subject matter;

FIGS. 46-53 are perspective views of the inserter of FIG. 44 showing theassembly of various components in accordance with the disclosed subjectmatter;

FIGS. 54-58 are cross-sectional views of the inserter of FIG. 44 inaccordance with the disclosed subject matter;

FIG. 59 illustrates a process for utilizing a sterilized version of theinserter of FIG. 44 in accordance with the disclosed subject matter;

FIG. 60 illustrates an alternate process for utilizing a sterilizedversion of the inserter of FIG. 44 in accordance with the disclosedsubject matter;

FIG. 61 is a perspective view of an inserter in accordance with thedisclosed subject matter;

FIGS. 62-66 are cross-sectional views of the inserter of FIG. 61 inaccordance with the disclosed subject matter;

FIGS. 67-69 are perspective views of components of the inserter of FIG.61 in accordance with the disclosed subject matter;

FIG. 70 is a perspective view of an inserter in accordance with thedisclosed subject matter;

FIG. 71 is a perspective view with parts separated of the inserter ofFIG. 70 in accordance with the disclosed subject matter; and

FIGS. 72-79 are cross-sectional views of the inserter of FIG. 70 inaccordance with the disclosed subject matter.

DETAILED DESCRIPTION OF THE EMBODIMENTS

A detailed description of the disclosure is provided herein. It shouldbe understood, in connection with the following description, that thesubject matter is not limited to particular embodiments described, asthe particular embodiments of the subject matter may, of course, vary.It is also to be understood that the terminology used herein is for thepurpose of describing particular embodiments only, and is not intendedto be limiting, since the scope of the disclosed subject matter will belimited only by the appended claims.

Where a range of values is provided, it is understood that eachintervening value between the upper and lower limit of that range, andany other stated or intervening value in that stated range, isencompassed within the disclosed subject matter. Every range stated isalso intended to specifically disclose each and every “subrange” of thestated range. That is, each and every range smaller than the outsiderange specified by the outside upper and outside lower limits given fora range, whose upper and lower limits are within the range from saidoutside lower limit to said outside upper limit (unless the contextclearly dictates otherwise), is also to be understood as encompassedwithin the disclosed subject matter, subject to any specificallyexcluded range or limit within the stated range. Where a range is statedby specifying one or both of an upper and lower limit, ranges excludingeither or both of those stated limits, or including one or both of them,are also encompassed within the disclosed subject matter, regardless ofwhether or not words such as “from,” “to,” “through,” or “including” areor are not used in describing the range.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this disclosed subject matter belongs. Although anymethods and materials similar or equivalent to those described hereincan also be used in the practice or testing of the present disclosedsubject matter, this disclosure may specifically mention certainexemplary methods and materials.

All publications mentioned in this disclosure are, unless otherwisespecified, incorporated by reference herein for all purposes, includingwithout limitation to disclose and describe the methods and/or materialsin connection with which the publications are cited.

The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present disclosedsubject matter is not entitled to antedate such publication by virtue ofprior invention. Further, the dates of publication provided may bedifferent from the actual publication dates, which may need to beindependently confirmed.

As used herein and in the appended claims, the singular forms “a,” “an,”and “the” include plural referents unless the context clearly dictatesotherwise.

Nothing contained in the Abstract or the Summary should be understood aslimiting the scope of the disclosure. The Abstract and the Summary areprovided for bibliographic and convenience purposes and due to theirformats and purposes should not be considered comprehensive.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentdisclosed subject matter. Any recited method can be carried out in theorder of events recited, or in any other order which is logicallypossible.

Reference to a singular item includes the possibility that there areplural of the same item present. When two or more items (for example,elements or processes) are referenced by an alternative “or,” thisindicates that either could be present separately or any combination ofthem could be present together except where the presence of onenecessarily excludes the other or others.

Generally, embodiments of the present disclosure relate to an apparatusfor inserting a medical device at least partially into the skin of thepatient. Some embodiments relate to in vivo methods and devices fordetecting at least one analyte such as glucose in body fluid.Accordingly, embodiments include in vivo analyte sensors configured sothat at least a portion of the sensor is positioned in the body of auser (e.g., within the ISF), to obtain information about at least oneanalyte of the body, e.g., transcutaneously positioned in user's body.In certain embodiments, an in vivo analyte sensor is coupled to anelectronics unit that is maintained on the body of the user to processinformation obtained from the sensor.

In certain embodiments, analyte information is communicated from a firstdevice such as an on body electronics unit to a second device which mayinclude user interface features, including a display, and/or the like.Information may be communicated from the first device to the seconddevice automatically and/or continuously when the analyte information isavailable, or may not be communicated automatically and/or continuously,but rather stored or logged in a memory of the first device.Accordingly, in many embodiments of the system, analyte informationderived by the sensor/on body electronics (for example, on bodyelectronics) is made available in a user-usable or viewable form onlywhen queried by the user such that the timing of data communication isselected by the user. In some embodiments, the display of information isselected by the user, while the timing of data communication is not.

In this manner, analyte information is only provided or evident to auser (provided at a user interface device) in some embodiments whendesired by the user even though an in vivo analyte sensor automaticallyand/or continuously monitors the analyte level in vivo, i.e., the sensorautomatically monitors analyte such as glucose on a pre-defined timeinterval over its usage life. For example, an analyte sensor may bepositioned in vivo and coupled to on body electronics for a givensensing period, e.g., about 14 days. In certain embodiments, thesensor-derived analyte information is automatically communicated fromthe sensor electronics assembly to a remote monitor device or displaydevice for output to a user throughout the 14 day period according to aschedule programmed at the on body electronics (e.g., about every 1minute or about every 5 minutes or about every 10 minutes, or the like).In certain embodiments, sensor-derived analyte information is onlycommunicated from the sensor electronics assembly to a remote monitordevice or display device at user-determined times, e.g., whenever a userdecides to check analyte information. At such times, a communicationssystem is activated and sensor-derived information is then sent from theon body electronics to the remote device or display device.

In still other embodiments, the information may be communicated from thefirst device to the second device automatically and/or continuously whenthe analyte information is available, and the second device stores orlogs the received information without presenting or outputting theinformation to the user. In such embodiments, the information isreceived by the second device from the first device when the informationbecomes available (e.g., when the sensor detects the analyte levelaccording to a time schedule). However, the received information isinitially stored in the second device and only output to a userinterface or an output component of the second device (e.g., display)upon detection of a request for the information on the second device.

Accordingly, in certain embodiments an inserter as described herein isused to place a sensor electronics assembly on the body so that at leasta portion of the in vivo sensor is in contact with bodily fluid such asISF. Once the sensor is electrically coupled to the electronics unit,sensor derived analyte information may be communicated from the on bodyelectronics to a display device on-demand by powering on the displaydevice (or it may be continually powered), and executing a softwarealgorithm stored in and accessed from a memory of the display device, togenerate one or more request commands, control signal or data packet tosend to the on body electronics. The software algorithm executed under,for example, the control of the microprocessor or application specificintegrated circuit (ASIC) of the display device may include routines todetect the position of the on body electronics relative to the displaydevice to initiate the transmission of the generated request command,control signal and/or data packet.

Display devices may also include programming stored in memory forexecution by one or more microprocessors and/or ASICs to generate andtransmit the one or more request command, control signal or data packetto send to the on body electronics in response to a user activation ofan input mechanism on the display device such as depressing a button onthe display device, triggering a soft button associated with the datacommunication function, and so on. The input mechanism may bealternatively or additionally provided on or in the on body electronicswhich may be configured for user activation. In certain embodiments,voice commands or audible signals may be used to prompt or instruct themicroprocessor or ASIC to execute the software routine(s) stored in thememory to generate and transmit the one or more request command, controlsignal or data packet to the on body device. In the embodiments that arevoice activated or responsive to voice commands or audible signals, onbody electronics and/or display device includes a microphone, a speaker,and processing routines stored in the respective memories of the on bodyelectronics and/or the display device to process the voice commandsand/or audible signals. In certain embodiments, positioning the on bodyelectronics and the display device within a predetermined distance(e.g., close proximity) relative to each other initiates one or moresoftware routines stored in the memory of the display device to generateand transmit a request command, control signal or data packet.

Different types and/or forms and/or amounts of information may be sentfor each on demand reading, including but not limited to one or more ofcurrent analyte level information (i.e., real time or the most recentlyobtained analyte level information temporally corresponding to the timethe reading is initiated), rate of change of an analyte over apredetermined time period, rate of the rate of change of an analyte(acceleration in the rate of change), historical analyte informationcorresponding to analyte information obtained prior to a given readingand stored in memory of the assembly. Some or all of real time,historical, rate of change, rate of rate of change (such as accelerationor deceleration) information may be sent to a display device for a givenreading. In certain embodiments, the type and/or form and/or amount ofinformation sent to a display device may be preprogrammed and/orunchangeable (e.g., preset at manufacturing), or may not bepreprogrammed and/or unchangeable so that it may be selectable and/orchangeable in the field one or more times (e.g., by activating a switchof the system, etc). Accordingly, in certain embodiments, for each ondemand reading, a display device will output a current (real time)sensor-derived analyte value (e.g., in numerical format), a current rateof analyte change (e.g., in the form of an analyte rate indicator suchas an arrow pointing in a direction to indicate the current rate), andanalyte trend history data based on sensor readings acquired by andstored in memory of on body electronics (e.g., in the form of agraphical trace). Additionally, the on skin or sensor temperaturereading or measurement associated with each on demand reading may becommunicated from the on body electronics to the display device. Thetemperature reading or measurement, however, may not be output ordisplayed on the display device, but rather, used in conjunction with asoftware routine executed by the display device to correct or compensatethe analyte measurement output to the user on the display device.

As described, embodiments include inserters for in vivo analyte sensorsand on body electronics that together provide body wearable sensorelectronics assemblies. In certain embodiments, in vivo analyte sensorsare fully integrated with on body electronics (fixedly connected duringmanufacture), while in other embodiments they are separate butconnectable post manufacture (e.g., before, during or after sensorinsertion into a body). On body electronics may include an in vivoglucose sensor, electronics, battery, and antenna encased (except forthe sensor portion that is for in vivo positioning) in a waterproofhousing that includes or is attachable to an adhesive pad. In certainembodiments, the housing withstands immersion in about one meter ofwater for up to at least 30 minutes. In certain embodiments, the housingwithstands continuous underwater contact, e.g., for longer than about 30minutes, and continues to function properly according to its intendeduse, e.g., without water damage to the housing electronics where thehousing is suitable for water submersion.

Embodiments include sensor insertion devices, which also may be referredto herein as sensor delivery units, or the like. Insertion devices mayretain on body electronics assemblies completely in an interiorcompartment, i.e., an insertion device may be “pre-loaded” with on bodyelectronics assemblies during the manufacturing process (e.g., on bodyelectronics may be packaged in a sterile interior compartment of aninsertion device). In such embodiments, insertion devices may formsensor assembly packages (including sterile packages) for pre-use or newon body electronics assemblies, and insertion devices configured toapply on body electronics assemblies to recipient bodies.

Embodiments include portable handheld display devices, as separatedevices and spaced apart from an on body electronics assembly, thatcollect information from the assemblies and provide sensor derivedanalyte readings to users. Such devices may also be referred to asmeters, readers, monitors, receivers, human interface devices,companions, or the like. Certain embodiments may include an integratedin vitro analyte meter. In certain embodiments, display devices includeone or more wired or wireless communications ports such as USB, serial,parallel, or the like, configured to establish communication between adisplay device and another unit (e.g., on body electronics, power unitto recharge a battery, a PC, etc). For example, a display devicecommunication port may enable charging a display device battery with arespective charging cable and/or data exchange between a display deviceand its compatible informatics software.

Compatible informatics software in certain embodiments include, forexample, but not limited to stand alone or network connection enableddata management software program, resident or running on a displaydevice, personal computer, a server terminal, for example, to performdata analysis, charting, data storage, data archiving and datacommunication as well as data synchronization. Informatics software incertain embodiments may also include software for executing fieldupgradable functions to upgrade firmware of a display device and/or onbody electronics unit to upgrade the resident software on the displaydevice and/or the on body electronics unit, e.g., with versions offirmware that include additional features and/or include software bugsor errors fixed, etc. Embodiments may include a haptic feedback featuresuch as a vibration motor or the like, configured so that correspondingnotifications (e.g., a successful on-demand reading received at adisplay device), may be delivered in the form of haptic feedback.

Embodiments include programming embedded on a computer readable medium,i.e., computer-based application software (may also be referred toherein as informatics software or programming or the like) thatprocesses analyte information obtained from the system and/or userself-reported data. Application software may be installed on a hostcomputer such as a mobile telephone, PC, an Internet-enabled humaninterface device such as an Internet-enabled phone, personal digitalassistant, or the like, by a display device or an on body electronicsunit. Informatics programming may transform data acquired and stored ona display device or on body unit for use by a user.

Embodiments of the subject disclosure are described primarily withrespect to glucose monitoring devices and systems, and methods ofglucose monitoring, for convenience only and such description is in noway intended to limit the scope of the disclosure. It is to beunderstood that the analyte monitoring system may be configured tomonitor a variety of analytes at the same time or at different times.

As described in detail below, embodiments include devices, systems, kitsand/or methods to monitor one or more physiological parameters such as,for example, but not limited to, analyte levels, temperature levels,heart rate, or user activity level, over a predetermined monitoring timeperiod. Also provided are methods of manufacturing. Predeterminedmonitoring time periods may be less than about 1 hour, or may includeabout 1 hour or more, e.g., about a few hours or more, e.g., about a fewdays of more, e.g., about 3 or more days, e.g., about 5 days or more,e.g., about 7 days or more, e.g., about 10 days or more, e.g., about 14days or more, e.g., about several weeks, e.g., about 1 month or more. Incertain embodiments, after the expiration of the predeterminedmonitoring time period, one or more features of the system may beautomatically deactivated or disabled at the on body electronicsassembly and/or display device.

For example, a predetermined monitoring time period may begin withpositioning the sensor in vivo and in contact with a body fluid such asISF, and/or with the initiation (or powering on to full operationalmode) of the on body electronics. Initialization of on body electronicsmay be implemented with a command generated and transmitted by a displaydevice in response to the activation of a switch and/or by placing thedisplay device within a predetermined distance (e.g., close proximity)to the on body electronics, or by user manual activation of a switch onthe on body electronics unit, e.g., depressing a button, or suchactivation may be caused by the insertion device, e.g., as described inU.S. patent application Ser. No. 12/698,129 filed on Feb. 1, 2010 andU.S. Provisional Application Nos. 61/238,646, 61/246,825, 61/247,516,61/249,535, 61/317,243, 61/345,562, and 61/361,374, the disclosures ofeach of which are incorporated herein by reference for all purposes.

When initialized in response to a received command from a displaydevice, the on body electronics retrieves and executes from its memorysoftware routine to fully power on the components of the on bodyelectronics, effectively placing the on body electronics in fulloperational mode in response to receiving the activation command fromthe display device. For example, prior to the receipt of the commandfrom the display device, a portion of the components in the on bodyelectronics may be powered by its internal power supply such as abattery while another portion of the components in the on bodyelectronics may be in powered down or maintained in a low power stateincluding no power state, inactive mode, or all components may be in aninactive, powered down mode. Upon receipt of the command, the remainingportion (or all) of the components of the on body electronics isswitched to active, fully operational mode.

Embodiments of on body electronics may include one or more printedcircuit boards with electronics including control logic implemented inASIC, microprocessors, memory, and the like, and transcutaneouslypositionable analyte sensors forming a single assembly. On bodyelectronics may be configured to provide one or more signals or datapackets associated with a monitored analyte level upon detection of adisplay device of the analyte monitoring system within a predeterminedproximity for a period of time (for example, about 2 minutes, e.g., 1minute or less, e.g., about 30 seconds or less, e.g., about 10 secondsor less, e.g., about 5 seconds or less, e.g., about 2 seconds or less)and/or until a confirmation, such as an audible and/or visual and/ortactile (e.g., vibratory) notification, is output on the display deviceindicating successful acquisition of the analyte related signal from theon body electronics. A distinguishing notification may also be outputfor unsuccessful acquisition in certain embodiments.

In certain embodiments, the monitored analyte level may be correlatedand/or converted to glucose levels in blood or other fluids such as ISF.Such conversion may be accomplished with the on body electronics, but inmany embodiments will be accomplished with display device electronics.In certain embodiments, glucose level is derived from the monitoredanalyte level in the ISF.

Analyte sensors may be insertable into a vein, artery, or other portionof the body containing analyte. In certain embodiments, analyte sensorsmay be positioned in contact with ISF to detect the level of analyte,where the detected analyte level may be used to infer the user's glucoselevel in blood or interstitial tissue.

Embodiments include transcutaneous sensors and also wholly implantablesensors and wholly implantable assemblies in which a single assemblyincluding the analyte sensor and electronics are provided in a sealedhousing (e.g., hermetically sealed biocompatible housing) forimplantation in a user's body for monitoring one or more physiologicalparameters.

Embodiments include analyte monitors that are provided in small,lightweight, battery-powered and electronically-controlled systems. Suchsystems may be configured to detect physical parameters of subjects,such as signals indicative of in vivo analyte levels using anelectrochemical sensor, and collect such signals, with or withoutprocessing. Any suitable measurement technique may be used to obtainsignals from the sensors, e.g., may detect current, may employpotentiometry, etc. Techniques may include, but are not limited toamperometry, coulometry, and voltammetry. In some embodiments, sensingsystems may be optical, colorimetric, and the like. In some embodiments,the portion of the system that performs this initial processing may beconfigured to provide the raw or at least initially processed data toanother unit for further collection and/or processing. Such provision ofdata may be affected, for example, by a wired connection, such as anelectrical, or by a wireless connection, such as an IR or RF connection.

In certain systems, the analyte sensor is in communication with on bodyelectronics. The on-body unit may include a housing in which the on bodyelectronics and at least a portion of the sensor are received.

Certain embodiments are modular. The on-body unit may be separatelyprovided as a physically distinct assembly from a monitor unit, e.g.,which displays or otherwise indicates analyte levels to a user. Theon-body unit may be configured to provide the analyte levels detected bythe sensor and/or other information (such as temperature, sensor life,etc.) over a communication link to the monitor unit. The monitor unit,in some embodiments, may include, e.g., a mobile telephone device, an invitro glucose meter, a personal digital assistant, or other consumerelectronics such as MP3 device, camera, radio, personal computer, etc.,or other communication-enabled data-processing device.

The display unit may perform a variety of functions such as but notlimited to data storage and/or processing and/or analysis and/orcommunication, etc., on the received analyte data to generateinformation pertaining to the monitored analyte levels and/or processthe other information. The monitor unit may incorporate a displayscreen, which can be used, for example, to display measured analytelevels, and/or an audio component such as a speaker to audibly provideinformation to a user, and/or a vibration device to provide tactilefeedback to a user. It is also useful for a user of ananalyte-monitoring system to be able to see trend indications (includingthe magnitude and direction of any ongoing trend, e.g., the rate ofchange of an analyte or other parameter, and the amount of time asubject is above and/or below a threshold, such as a hypoglycemic and/orhyperglycemic threshold, etc.); such data may be displayed eithernumerically, or by a visual indicator such as an arrow that may vary invisual attributes, like size, shape, color, animation, or direction. Themonitor unit may further be adapted to receive information from or aboutan in vitro analyte test strip, which may be manually or automaticallyentered into the monitor unit. In some embodiments a monitor unit mayincorporate an in vitro analyte test strip port and related electronicsin order to be able to make discrete (e.g., blood glucose) measurementsusing an in vitro test strip (see, e.g., U.S. Pat. No. 6,175,752, thedisclosure of which is incorporated by reference herein for allpurposes).

The modularity of these systems may vary where one or more componentsmay be constructed to be single use and one or more may be constructedto be re-useable. In some embodiments the sensor is designed to beattachable and detachable from the on body electronics (and the on-bodyunit may be reusable), e.g., so that one or more of the components maybe reused one or more times, while in other embodiments, the sensor andon body electronics may be provided as an integrated, undetachablepackage, which may be designed to be disposable after use, i.e., notre-used.

Embodiments of In Vivo Monitoring Systems

For purpose of illustration, and not limitation, the inserters describedherein may be used in connection with an exemplary analyte monitoringsystem as depicted in FIG. 1. It is understood that the insertersdescribed herein may be used with any medical device on its own or inconnection with a system. FIG. 1 shows an exemplary in vivo-basedanalyte monitoring system 1000 in accordance with embodiments of thepresent disclosure. As shown, in certain embodiments, analyte monitoringsystem 1000 includes on body electronics 1100 electrically coupled to invivo analyte sensor 14 (a proximal portion of which is shown in FIG. 1),and attached to adhesive layer 218 for attachment on a skin surface onthe body of a user. On body electronics 1100 includes on body housing122 that defines an interior compartment.

Also shown in FIG. 1 is insertion device 200 (or insertion devices 300,400, 2400, 2500, 2700, 3700 described herein) that, when operated,transcutaneously positions a portion of analyte sensor 14 through a skinsurface and in fluid contact with ISF, and positions on body electronics1100 and adhesive layer 218 on a skin surface, as will be described ingreater detail herein. In certain embodiments, on body electronics 1100,analyte sensor 14 and adhesive layer 218 are sealed within the housingof insertion device 200 before use, and in certain embodiments, adhesivelayer 218 is also sealed within the housing or the adhesive layer canprovide a seal for preserving the sterility of the apparatus. Additionaldetails regarding insertion devices are discussed, e.g., in U.S. patentapplication Ser. No. 12/698,129 and U.S. Provisional Application Nos.61/238,646, 61/246,825, 61/247,516, 61/249,535, and 61/345,562, thedisclosures of each of which are incorporated herein by reference forall purposes.

Referring back to the FIG. 1, analyte monitoring system 1000 includesdisplay device 1200 which includes a display 1220 to output informationto the user, an input component 1210 such as a button, actuator, a touchsensitive switch, a capacitive switch, pressure sensitive switch, jogwheel or the like, to input data or command to display device 1200 orotherwise control the operation of display device 1200. It is noted thatsome embodiments may include display-less devices or devices without anyuser interface components. These devices may be functionalized to storedata as a data logger and/or provide a conduit to transfer data from onbody electronics and/or a display-less device to another device and/orlocation. Embodiments will be described herein as display devices forexemplary purposes which are in no way intended to limit the embodimentsof the present disclosure. It will be apparent that display-less devicesmay also be used in certain embodiments.

In certain embodiments, on body electronics 1100 may be configured tostore some or all of the monitored analyte related data received fromanalyte sensor 14 in a memory during the monitoring time period, andmaintain it in memory until the usage period ends. In such embodiments,stored data is retrieved from on body electronics 1100 at the conclusionof the monitoring time period, for example, after removing analytesensor 14 from the user by detaching on body electronics 1100 from theskin surface where it was positioned during the monitoring time period.In such data logging configurations, real time monitored analyte levelis not communicated to display device 1200 during the monitoring periodor otherwise transmitted from on body electronics 1100, but rather,retrieved from on body electronics 1100 after the monitoring timeperiod.

In certain embodiments, input component 1210 of display device 1200 mayinclude a microphone and display device 1200 may include softwareconfigured to analyze audio input received from the microphone, suchthat functions and operation of the display device 1200 may becontrolled by voice commands. In certain embodiments, an outputcomponent of display device 1200 includes a speaker for outputtinginformation as audible signals. Similar voice responsive components suchas a speaker, microphone and software routines to generate, process andstore voice driven signals may be provided to on body electronics 1100.

In certain embodiments, display 1220 and input component 1210 may beintegrated into a single component, for example a display that candetect the presence and location of a physical contact touch upon thedisplay such as a touch screen user interface. In such embodiments, theuser may control the operation of display device 1200 by utilizing a setof pre-programmed motion commands, including, but not limited to, singleor double tapping the display, dragging a finger or instrument acrossthe display, motioning multiple fingers or instruments toward oneanother, motioning multiple fingers or instruments away from oneanother, etc. In certain embodiments, a display includes a touch screenhaving areas of pixels with single or dual function capacitive elementsthat serve as LCD elements and touch sensors.

Display device 1200 also includes data communication port 1230 for wireddata communication with external devices such as remote terminal(personal computer) 1700, for example. Example embodiments of the datacommunication port 1230 include USB port, mini USB port, RS-232 port,Ethernet port, Firewire port, or other similar data communication portsconfigured to connect to the compatible data cables. Display device 1200may also include an integrated in vitro glucose meter, including invitro test strip port 1240 to receive an in vitro glucose test strip forperforming in vitro blood glucose measurements.

Referring still to FIG. 1, display 1220 in certain embodiments isconfigured to display a variety of information—some or all of which maybe displayed at the same or different time on display 1220. In certainembodiments the displayed information is user-selectable so that a usercan customize the information shown on a given display screen. Display1220 may include but is not limited to graphical display 1380, forexample, providing a graphical output of glucose values over a monitoredtime period (which may show important markers such as meals, exercise,sleep, heart rate, blood pressure, etc, numerical display 1320, forexample, providing monitored glucose values (acquired or received inresponse to the request for the information), and trend or directionalarrow display 1310 that indicates a rate of analyte change and/or a rateof the rate of analyte change, e.g., by moving locations on display1220.

As further shown in FIG. 1, display 1220 may also include date display1350 providing for example, date information for the user, time of dayinformation display 1390 providing time of day information to the user,battery level indicator display 1330 which graphically shows thecondition of the battery (rechargeable or disposable) of the displaydevice 1200, sensor calibration status icon display 1340 for example, inmonitoring systems that require periodic, routine or a predeterminednumber of user calibration events, notifying the user that the analytesensor calibration is necessary, audio/vibratory settings icon display1360 for displaying the status of the audio/vibratory output or alarmstate, and wireless connectivity status icon display 1370 that providesindication of wireless communication connection with other devices suchas on body electronics, data processing module 1600, and/or remoteterminal 1700. As additionally shown in FIG. 1, display 1220 may furtherinclude simulated touch screen button 1250, 1260 for accessing menus,changing display graph output configurations or otherwise forcontrolling the operation of display device 1200.

Referring back to FIG. 1, in certain embodiments, display 1220 ofdisplay device 1200 may be additionally, or instead of visual display,configured to output alarms notifications such as alarm and/or alertnotifications, glucose values etc, which may be audible, tactile, or anycombination thereof. In one aspect, the display device 1200 may includeother output components such as a speaker, vibratory output componentand the like to provide audible and/or vibratory output indication tothe user in addition to the visual output indication provided on display1220. Further details and other display embodiments can be found in,e.g., U.S. patent application Ser. No. 12/871,901, U.S. provisionalapplication Nos. 61/238,672, 61/247,541, 61/297,625, the disclosures ofeach of which are incorporated herein by reference for all purposes.

After the positioning of on body electronics 1100 on the skin surfaceand analyte sensor 14 in vivo to establish fluid contact with ISF (orother appropriate body fluid), on body electronics 1100 in certainembodiments is configured to wirelessly communicate analyte related data(such as, for example, data corresponding to monitored analyte leveland/or monitored temperature data, and/or stored historical analyterelated data) when on body electronics 1100 receives a command orrequest signal from display device 1200. In certain embodiments, on bodyelectronics 1100 may be configured to at least periodically broadcastreal time data associated with monitored analyte level which is receivedby display device 1200 when display device 1200 is within communicationrange of the data broadcast from on body electronics 1100, i.e., it doesnot need a command or request from a display device to send information.

For example, display device 1200 may be configured to transmit one ormore commands to on body electronics 1100 to initiate data transfer, andin response, on body electronics 1100 may be configured to wirelesslytransmit stored analyte related data collected during the monitoringtime period to display device 1200. Display device 1200 may in turn beconnected to a remote terminal 1700 such as a personal computer andfunctions as a data conduit to transfer the stored analyte levelinformation from the on body electronics 1100 to remote terminal 1700.In certain embodiments, the received data from the on body electronics1100 may be stored (permanently or temporarily) in one or more memory ofthe display device 1200. In certain other embodiments, display device1200 is configured as a data conduit to pass the data received from onbody electronics 1100 to remote terminal 1700 that is connected todisplay device 1200.

Referring still to FIG. 1, also shown in analyte monitoring system 1000are data processing module 1600 and remote terminal 1700. Remoteterminal 1700 may include a personal computer, a server terminal alaptop computer or other suitable data processing devices includingsoftware for data management and analysis and communication with thecomponents in the analyte monitoring system 1000. For example, remoteterminal 1700 may be connected to a local area network (LAN), a widearea network (WAN), or other data network for uni-directional orbi-directional data communication between remote terminal 1700 anddisplay device 1200 and/or data processing module 1600.

Remote terminal 1700 in certain embodiments may include one or morecomputer terminals located at a physician's office or a hospital. Forexample, remote terminal 1700 may be located at a location other thanthe location of display device 1200. Remote terminal 1700 and displaydevice 1200 could be in different rooms or different buildings. Remoteterminal 1700 and display device 1200 could be at least about one mileapart, e.g., at least about 100 miles apart, e.g., at least about 1000miles apart. For example, remote terminal 1700 could be in the same cityas display device 1200, remote terminal 1700 could be in a differentcity than display device 1200, remote terminal 1700 could be in the samestate as display device 1200, remote terminal 1700 could be in adifferent state than display device 1200, remote terminal 1700 could bein the same country as display device 1200, or remote terminal 1700could be in a different country than display device 1200, for example.

In certain embodiments, a separate, optional datacommunication/processing device such as data processing module 1600 maybe provided in analyte monitoring system 1000. Data processing module1600 may include components to communicate using one or more wirelesscommunication protocols such as, for example, but not limited to,infrared (IR) protocol, Bluetooth® protocol, Zigbee® protocol, and802.11 wireless LAN protocol. Additional description of communicationprotocols including those based on Bluetooth® protocol and/or Zigbee®protocol can be found in U.S. Patent Publication No. 2006/0193375incorporated herein by reference for all purposes. Data processingmodule 1600 may further include communication ports, drivers orconnectors to establish wired communication with one or more of displaydevice 1200, on body electronics 1100, or remote terminal 1700including, for example, but not limited to USB connector and/or USBport, Ethernet connector and/or port, FireWire connector and/or port, orRS-232 port and/or connector.

In certain embodiments, data processing module 1600 is programmed totransmit a polling or query signal to on body electronics 1100 at apredetermined time interval (e.g., once every minute, once every fiveminutes, or the like), and in response, receive the monitored analytelevel information from on body electronics 1100. Data processing module1600 stores in its memory the received analyte level information, and/orrelays or retransmits the received information to another device such asdisplay device 1200. More specifically in certain embodiments, dataprocessing module 1600 may be configured as a data relay device toretransmit or pass through the received analyte level data from on bodyelectronics 1100 to display device 1200 or a remote terminal (forexample, over a data network such as a cellular or WiFi data network) orboth.

In certain embodiments, on body electronics 1100 and data processingmodule 1600 may be positioned on the skin surface of the user within apredetermined distance of each other (for example, about 1-12 inches, orabout 1-10 inches, or about 1-7 inches, or about 1-5 inches) such thatperiodic communication between on body electronics 1100 and dataprocessing module 1600 is maintained. Alternatively, data processingmodule 1600 may be worn on a belt or clothing item of the user, suchthat the desired distance for communication between the on bodyelectronics 1100 and data processing module 1600 for data communicationis maintained. In a further aspect, the housing of data processingmodule 1600 may be configured to couple to or engage with on bodyelectronics 1100 such that the two devices are combined or integrated asa single assembly and positioned on the skin surface. In furtherembodiments, data processing module 1600 is detachably engaged orconnected to on body electronics 1100 providing additional modularitysuch that data processing module 1600 may be optionally removed orreattached as desired.

Referring again to FIG. 1, in certain embodiments, data processingmodule 1600 is programmed to transmit a command or signal to on bodyelectronics 1100 at a predetermined time interval such as once everyminute, or once every 5 minutes or once every 30 minutes or any othersuitable or desired programmable time interval to request analyterelated data from on body electronics 1100. When data processing module1600 receives the requested analyte related data, it stores the receiveddata. In this manner, analyte monitoring system 1000 may be configuredto receive the continuously monitored analyte related information at theprogrammed or programmable time interval, which is stored and/ordisplayed to the user. The stored data in data processing module 1600may be subsequently provided or transmitted to display device 1200,remote terminal 1700 or the like for subsequent data analysis such asidentifying frequency of periods of glycemic level excursions over themonitored time period, or the frequency of the alarm event occurrenceduring the monitored time period, for example, to improve therapyrelated decisions. Using this information, the doctor, healthcareprovider or the user may adjust or recommend modification to the diet,daily habits and routines such as exercise, and the like.

In another embodiment, data processing module 1600 transmits a commandor signal to on body electronics 1100 to receive the analyte relateddata in response to a user activation of a switch provided on dataprocessing module 1600 or a user initiated command received from displaydevice 1200. In further embodiments, data processing module 1600 isconfigured to transmit a command or signal to on body electronics 1100in response to receiving a user initiated command only after apredetermined time interval has elapsed. For example, in certainembodiments, if the user does not initiate communication within aprogrammed time period, such as, for example about 5 hours from lastcommunication (or 10 hours from the last communication, or 24 hours fromthe last communication), the data processing module 1600 may beprogrammed to automatically transmit a request command or signal to onbody electronics 1100. Alternatively, data processing module 1600 may beprogrammed to activate an alarm to notify the user that a predeterminedtime period of time has elapsed since the last communication between thedata processing module 1600 and on body electronics 1100. In thismanner, users or healthcare providers may program or configure dataprocessing module 1600 to provide certain compliance with analytemonitoring regimen, so that frequent determination of analyte levels ismaintained or performed by the user.

In certain embodiments, when a programmed or programmable alarmcondition is detected (for example, a detected glucose level monitoredby analyte sensor 14 that is outside a predetermined acceptable rangeindicating a physiological condition) which requires attention orintervention for medical treatment or analysis (for example, ahypoglycemic condition, a hyperglycemic condition, an impendinghyperglycemic condition or an impending hypoglycemic condition), the oneor more output indications may be generated by the control logic orprocessor of the on body electronics 1100 and output to the user on auser interface of on body electronics 1100 so that corrective action maybe timely taken. In addition to or alternatively, if display device 1200is within communication range, the output indications or alarm data maybe communicated to display device 1200 whose processor, upon detectionof the alarm data reception, controls the display 1220 to output one ormore notification.

In certain embodiments, control logic or microprocessors of on bodyelectronics 1100 include software programs to determine future oranticipated analyte levels based on information obtained from analytesensor 14, e.g., the current analyte level, the rate of change of theanalyte level, the acceleration of the analyte level change, and/oranalyte trend information determined based on stored monitored analytedata providing a historical trend or direction of analyte levelfluctuation as function time during monitored time period. Predictivealarm parameters may be programmed or programmable in display device1200, or the on body electronics 1100, or both, and output to the userin advance of anticipating the user's analyte level reaching the futurelevel. This provides the user an opportunity to take timely correctiveaction.

Information, such as variation or fluctuation of the monitored analytelevel as a function of time over the monitored time period providinganalyte trend information, for example, may be determined by one or morecontrol logic or microprocessors of display device 1200, data processingmodule 1600, and/or remote terminal 1700, and/or on body electronics1100. Such information may be displayed as, for example, a graph (suchas a line graph) to indicate to the user the current and/or historicaland/or and predicted future analyte levels as measured and predicted bythe analyte monitoring system 1000. Such information may also bedisplayed as directional arrows (for example, see trend or directionalarrow display 1310) or other icon(s), e.g., the position of which on thescreen relative to a reference point indicated whether the analyte levelis increasing or decreasing as well as the acceleration or decelerationof the increase or decrease in analyte level. This information may beutilized by the user to determine any necessary corrective actions toensure the analyte level remains within an acceptable and/or clinicallysafe range. Other visual indicators, including colors, flashing, fading,etc., as well as audio indicators including a change in pitch, volume,or tone of an audio output and/or vibratory or other tactile indicatorsmay also be incorporated into the display of trend data as means ofnotifying the user of the current level and/or direction and/or rate ofchange of the monitored analyte level. For example, based on adetermined rate of glucose change, programmed clinically significantglucose threshold levels (e.g., hyperglycemic and/or hypoglycemiclevels), and current analyte level derived by an in vivo analyte sensor,the system 1000 may include an algorithm stored on computer readablemedium to determine the time it will take to reach a clinicallysignificant level and will output notification in advance of reachingthe clinically significant level, e.g., 30 minutes before a clinicallysignificant level is anticipated, and/or 20 minutes, and/or 10 minutes,and/or 5 minutes, and/or 3 minutes, and/or 1 minute, and so on, withoutputs increasing in intensity or the like.

Referring again back to FIG. 1, in certain embodiments, softwarealgorithm(s) for execution by data processing module 1600 may be storedin an external memory device such as an SD card, microSD card, compactflash card, XD card, Memory Stick card, Memory Stick Duo card, or USBmemory stick/device including executable programs stored in such devicesfor execution upon connection to the respective one or more of the onbody electronics 1100, remote terminal 1700 or display device 1200. In afurther aspect, software algorithms for execution by data processingmodule 1600 may be provided to a communication device such as a mobiletelephone including, for example, WiFi or Internet enabled smart phonesor personal digital assistants (PDAs) as a downloadable application forexecution by the downloading communication device.

Examples of smart phones include Windows®, Android™, iPhone® operatingsystem, Palm® WebOS™, Blackberry® operating system, or Symbian®operating system based mobile telephones with data network connectivityfunctionality for data communication over an internet connection and/ora local area network (LAN). PDAs as described above include, forexample, portable electronic devices including one or moremicroprocessors and data communication capability with a user interface(e.g., display/output unit and/or input unit, and configured forperforming data processing, data upload/download over the internet, forexample. In such embodiments, remote terminal 1700 may be configured toprovide the executable application software to the one or more of thecommunication devices described above when communication between theremote terminal 1700 and the devices are established.

In still further embodiments, executable software applications may beprovided over-the-air (OTA) as an OTA download such that wiredconnection to remote terminal 1700 is not necessary. For example,executable applications may be automatically downloaded as softwaredownload to the communication device, and depending upon theconfiguration of the communication device, installed on the device foruse automatically, or based on user confirmation or acknowledgement onthe communication device to execute the installation of the application.The OTA download and installation of software may include softwareapplications and/or routines that are updates or upgrades to theexisting functions or features of data processing module 1600 and/ordisplay device 1200.

Referring back to remote terminal 1700 of FIG. 1, in certainembodiments, new software and/or software updates such as softwarepatches or fixes, firmware updates or software driver upgrades, amongothers, for display device 1200 and/or on body electronics 1100 and/ordata processing module 1600 may be provided by remote terminal 1700 whencommunication between the remote terminal 1700 and display device 1200and/or data processing module 1600 is established. For example, softwareupgrades, executable programming changes or modification for on bodyelectronics 1100 may be received from remote terminal 1700 by one ormore of display device 1200 or data processing module 1600, andthereafter, provided to on body electronics 1100 to update its softwareor programmable functions. For example, in certain embodiments, softwarereceived and installed in on body electronics 1100 may include softwarebug fixes, modification to the previously stalled software parameters(modification to analyte related data storage time interval, resettingor adjusting time base or information of on body electronics 1100,modification to the transmitted data type, data transmission sequence,or data storage time period, among others). Additional detailsdescribing field upgradability of software of portable electronicdevices, and data processing are provided in U.S. application Ser. Nos.12/698,124, 12/794,721, now U.S. Pat. No. 8,595,607, Ser. Nos.12/699,653, and 12/699,844, and U.S. Provisional Application Nos.61/359,265 and 61/325,155 the disclosures of which are incorporated byreference herein for all purposes.

The Sensor

The analyte sensor 14 of the analyte measurement system 1000 may be usedto monitor levels of a wide variety of analytes. Analytes that may bemonitored include, for example, acetylcholine, amylase, bilirubin,cholesterol, chorionic gonadotropin, creatine kinase (e.g., CK-MB),creatine, DNA, fructosamine, glucose, glutamine, growth hormones,hormones, ketones, lactate, peroxide, prostate-specific antigen,prothrombin, RNA, thyroid-stimulating hormone, and troponin. Theconcentration of drugs, such as, for example, antibiotics (e.g.,gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs ofabuse, theophylline, and warfarin, may also be monitored. One or moreanalyte may be monitored by a given sensor. In those embodiments thatmonitor more than one analyte, the analytes may be monitored at the sameor different times, which may use the same on body electronics (e.g.,simultaneously) or with different on body electronics.

In one embodiment of the present disclosure, sensor 14 is physicallypositioned in or on the body of a user whose analyte level is beingmonitored. Sensor 14 may be configured to continuously sample theanalyte level of the user and convert the sampled analyte level, e.g.,glucose concentration into a corresponding data signal, e.g., a currentor voltage, for input into on body electronics. Alternatively, sensor 14may be configured to sample analyte levels on demand. The on bodyelectronics may amplify, filter, average, and/or otherwise processsignal provided by the sensor.

An embodiment of the sensor 14 is illustrated in FIG. 2. It isunderstood that the inserters described herein can be used with othermedical devices. The shape(s) described herein are exemplary only. Othersensor shapes are contemplated. In some embodiments, sensor 14 includesa substrate which is a dielectric, e.g., a polymer or plastic material,such as polyester or polyamide. In this embodiment, the sensor isconstructed so that a portion is positionable beneath skin and a portionis above skin. Accordingly, sensor 14 includes an insertion or internalportion 30 and an external or electrical contact portion 32. In someembodiments, the contact portion 32 includes several conductive contacts36, 38, and 40 (herein shown as three contacts) for connection to otherelectronics, e.g., at the on body electronics 1100. (See FIG. 1.) Thecontacts provided in this embodiment are for a working electrode, areference electrode, and a counter electrode. In some embodiments, twoor more working electrodes are provided. The operative portions of theseelectrodes, that is, working electrode, reference electrode, and counterelectrode (not individually shown), are provided at the insertionportion, e.g., at the distal end of insertion portion 30, e.g., portion34. In some embodiments, one or more electrodes may be external to thebody, e.g., an external counter electrode. The contact and operativeportions of the electrodes are connected by circuit traces 42, 44, and46 running on the surface of the substrate. In some embodiments, thetraces are provided in channels, or may be embedded within thesubstrate, or may traverse different sides of the substrate. Theconductive contacts, conductive traces, and electrodes are fabricatedfrom conductive material, such as platinum, palladium, gold, carbon, orthe like. More than one material may be used for a given sensor. Furtherdetails of sensors are described, e.g., in U.S. Pat. Nos. 6,175,572 and6,103,033, which are incorporated by reference herein for all purposes.

Sensor 14 may include a proximal retention portion 48. The insertionportion 30 and the proximal retention portion 48 are sized andconfigured to be positioned with a sharp for installation into the skinof a subject, as described herein. In use, the sensor 14 may beconfigured to bend (e.g., along the line B) and therefore be positionedin two substantially perpendicular, intersecting planes. Such bendingmay occur prior to or during coupling to the on body electronics asdescribed below. (See FIG. 17).

Portions 48 and 52 provide a path for electrical connections, e.g., theconductive traces, between the proximal and distal portions of thesensor. Sensor 14 is further provided with a notch or cut-out 54. Suchconfiguration facilitates the sensor 14 to bend (e.g., along the lineindicated by line B) such that retention portion 48 remains upright andtherefore be positioned in two substantially perpendicular, intersectingplanes, as illustrated in FIG. 3. As will be described below, the sensortab 50 can be encased in the on body housing 122 to aid in securing andpositioning the sensor 14. Proximal retention portion 48 maintains itslongitudinal alignment with insertion portion 30 for positioning withinan insertion sharp.

Embodiments of analyte sensors have been described herein to operateelectrochemically, through an arrangement of electrodes having chemicalsensing layers applied thereto, by generating an electrical currentproportional to the volume of a redox reaction of the analyte (andindicative of analyte concentration), catalyzed by an analyte-specificoxidizing enzyme. Embodiments exist in which the number of electrodesprovided to bring about and detect the level of these reactions is two,three, or a greater number. However, other types of sensors may beemployed as described herein.

A portion of sensor 14 may be situated above the surface of the skin,with a distal portion 30 penetrating through the skin and into thesubcutaneous space in contact with the user's biofluid, such as ISF.Further details regarding the electrochemistry of sensor 14 is providedin U.S. Pat. Nos. 5,264,104; 5,356,786; 5,262,035; 5,320,725; and6,990,366, each of which is incorporated by reference herein for allpurposes.

In some embodiments, the sensor is implantable into a subject's body fora usage period (e.g., a minute or more, at least one day or more, aboutone to about 30 days or even longer, about three to about fourteen days,about three to about seven days, or in some embodiments, longer periodsof up to several weeks) to contact and monitor an analyte present in abiological fluid. In this regard, the sensor can be disposed in asubject at a variety of sites (e.g., abdomen, upper arm, thigh, etc.),including intramuscularly, transcutaneously, intravascularly, or in abody cavity.

In some embodiments, sensor 14 is employed by insertion and/orimplantation into a user's body for some usage period. In suchembodiments, the substrate may be formed from a relatively flexiblematerial.

While the embodiments illustrated in FIGS. 2-3 have three electrodes,other embodiments can include a fewer or greater number of electrodes.For example, a two-electrode sensor can be utilized. The sensor 14 maybe externally-powered and allow a current to pass which is proportionalto the amount of analyte present. Alternatively, the sensor 14 itselfmay act as a current source in some embodiments. In some two-electrodeembodiments, the sensor may be self-biasing and there may be no need fora reference electrode. An exemplary self-powered, two-electrode sensoris described in U.S. patent application Ser. No. 12/393,921, filed Feb.26, 2009, and entitled “Self-Powered Analyte Sensor,” which is herebyincorporated by reference herein for all purposes. The level of currentprovided by a self-powered sensor may be low, for example, on the orderof nanoamperes, in certain embodiments.

Insertion Assembly

Insertion assemblies are provided, which are used to install a medicaldevice to the subject. In some embodiments, an insertion assemblyincludes an inserter and the medical device itself. The inserter can beconfigured to insert various medical devices into the subject, such asfor example, an analyte sensor, an infusion set, or a cannula. In someembodiments, the inserter can be configured to install a combination ofsuch devices, e.g., a combined sensor/infusion set, etc., at the same ordifferent times or locations. For example, in certain embodiments agiven inserter can be configured to install a first device and a seconddevice at different times. In this regard, the inserter can be reusable.For example, an inserter may be modifiable to be used with more than onemedical device, to include more than one type of medical device, e.g.,by attaching an adapter and/or detaching a portion of an inserter. Theinserter can install the medical device in, under, or through the skinof the subject, or place the medical device on the surface of the skin.The medical device can include features or structures, e.g., barbs,tabs, adhesive, etc., to maintain the device in position with respect tothe skin after insertion. The inserter device may also be used as alancet, e.g., to pierce the skin without inserting or installing amedical device.

In some embodiments, an insertion assembly includes an inserter, ananalyte sensor, and a power supply. The power supply may be insertedsimultaneously with the analyte sensor by the inserter. In otherembodiments, the battery is installed after or before installation ofthe analyte sensor. In such case the power supply may be applied by theinserter or separately. The power supply may be used to provide acurrent or a potential to the sensor and/or to provide power forcommunication of one or more signals to the monitor unit.

In some embodiments, an insertion assembly includes an inserter, amedical device such as an analyte sensor, and on-body electronics. Theon-body electronics may be deployed and/or installed simultaneously withthe analyte sensor by the inserter. In other embodiments, the on-bodyelectronics are installed after or before installation of the analytesensor. For example, the analyte sensor may be installed by theinserter, and the on-body electronics may be subsequently installed.

In some embodiments, the on-body electronics provide a voltage orcurrent to the analyte sensor. In some embodiments, the on-bodyelectronics process signals provided by the analyte sensor. In furtherembodiments, the on-body electronics may include communicationsfunctionality for providing signal relating to signal provided by theanalyte sensor to a further component, such as, e.g., a monitor unit, acomputer, or other component. In some embodiments, communicationscircuitry, such as an RFID antenna, is provided. The power supply may beused to power some or all of these functions. In some embodiments, poweris provided from the monitor unit, e.g., via inductive coupling.

An inserter can include a plurality of different components. Forexample, an inserter may include one or more components for advancing asharp towards the skin of the subject. The sensor and on-bodyelectronics may be supported by a support structure, such as a carriage.A driver may be provided for advancing the sharp and/or the analytesensor/support structure. In some embodiments, the actuator is directlyor indirectly coupled to the sharp and/or support structure, such thatmanual force applied by the user to the actuator is transferred to thesharp and/or support structure. In some embodiments, the applied forcedrives the sharp and/or support structure between a retracted position(within the inserter) and an advanced position (towards the skin of thesubject). In some embodiments, the sensor and on-body electronics ismaintained in a retracted position prior to installation by contactingprojections extending inwardly from a sheath. In accordance with thisembodiment, the sensor and on-body electronics are temporarilymaintained operatively between the support structure and the projectionsdisposed on the interior wall of the sheath.

An inserter can also include one or more components for retracting thesharp, while allowing the analyte sensor and optional on-bodyelectronics to remain on the subject. The components for retracting thesharp can include a retractor. It is understood that the retractor andthe actuator may be the same structure or include some commoncomponents. In some embodiments, the retractor is directly or indirectlycoupled to the sharp such that the manual force applied by the user istransferred from the retractor to the sharp to retract the sharp fromthe skin. In other embodiments, a drive assembly may be provided toretract the sharp. For example, the drive assembly may include a spring,motor, hydraulic piston, etc., to retract the sharp away from the skinof the subject. The drive assembly may also include a linear drivecomponent.

In some embodiments, the retractor withdraws the sharp upon actuation bythe user. In such cases, the user actuates the retractor when it isdesired to withdraw the sharp. For example, the retractor may include arelease switch. Upon activation of the release switch, the driveassembly, e.g., the spring or other driver, retracts the sharp from theskin. In other embodiments, the retractor and the actuator includecommon components. After activating the actuator to advance the sharpand the analyte sensor, the user releases the actuator, which allows thedrive assembly to withdraw the sharp from the skin.

In some embodiments, the retractor withdraws the sharp without furtheruser interaction after actuation of insertion. For example, the insertermay include features or components which automatically retract the sharpupon advancement of the sharp and support structure by a predeterminedamount. Inserter devices, in which no further action by the user isrequired to initiate withdrawal of the sharp after insertion, arereferred to herein as having “automatic” withdrawal of the sharp.

Inserter Devices

One embodiment of a needle hub for an inserter is illustrated in FIGS.4-5. Needle hub 136 supports sharp 124, having a sharpened distalportion 160. In some embodiments, as discussed herein, a longitudinalwall opening or gap 162 is provided in at least a portion of the wall ofthe sharp 124. The length N of the gap 162 is selected to becommensurate with the length of the insertion portion 30 through to theproximal retention portion 48 of the sensor, and in certain embodimentsmay be about 3 mm to about 50 mm, e.g., about 5 mm, or about 10 mm, orabout 15 mm, or about 20 mm. The length L of the sharp 124 may be about3 mm to about 50 mm, e.g., 5 mm or more, or about 10 mm, or about 20 mm,or about 30 mm, or about 50 mm, and is selected based upon the length ofthe insertion portion 30 of a sensor and the desired depth of theinsertion portion 30 of the sensor 14. In some embodiments, the distanceor spacing between the two edges of the gap is about 0.2 mm to about 0.5mm, e.g., about 0.22 mm, about 0.25 mm, etc.

The distal portion 160 of sharp 124 is illustrated in greater detail inFIGS. 6-8. As illustrated in FIG. 6, sharp 124 has a substantially “C”-or “U”-shaped profile in this embodiment, but may have otherconfigurations, e.g., substantially “V”-shaped. A longitudinal gap 162is provided in the wall of the sharp 124. FIG. 7 illustrates distalportion 160 is provided with an angled tip. In some embodiments, theangled tip may be provided with a first angled tip portion 164 and asecond steep-angled tip portion 166. The exemplary configuration, whichincludes multiple edges and faces, provides a sharp point to reducepenetration force, trauma, and bleeding for the subject. The distalsection of the sensor body has a width sized to fit within the gap 162of the insertion sharp 124 having a diameter less than about 20 to about26 gauge, e.g., 21 gauge to about 25 gauge, where in certain embodimentsthe sharp is 21 gauge or 23 gauge or 25 gauge. Such sharp may be usedwith a sensor having a width or diameter —at least the portion that iscarried by the sharp—of about 0.20 mm to about 0.80 mm, e.g., about 0.25mm to about 0.60 mm, where in some embodiments the width or diameter ofat least a portion of a sensor is 0.27 mm or 0.33 mm or 0.58 mm. In someembodiments, sharp 124 is fabricated from a sheet of metal and foldedinto a substantially “V,” “U” or “C” configuration in cross-section.Various technologies can be used to manufacture a folded sheet of metalto form sharp 124. For example, etched-sheet metal technology can beused to form the sharp 124. In this manner, the sharp can be formedhaving a very sharp edge so that penetration through the skin duringinsertion is less painful. In other embodiments, a progressive dietechnology may be utilized to form a complex sheet-metal shape that hasa sharp edge as depicted in FIG. 9. In some embodiments, the sharp 124can be molded with a plastic cap so that the sharp can be handled duringthe inserter assembly process. Further, the die cut sharp may be moldedwith plastic to reinforce the “V,” “U” or “C” shaped sheet metalconfiguration. In other embodiments, a laser-cut sharp can be formed. Inthis manner, the laser can be used to form the wall opening or gap 162and first-angled tip portion 164 and a second, steep-angled tip portion166.

In another embodiment, a sharp 124 may be formed from a standardhypodermic needle utilizing the method depicted in FIG. 10. First, thehypodermic needle (having a circular cross-section) is cut to thedesired length for sharp 124. Next, the hypodermic needle is compressedso that its cross-section is permanently deformed from a circular shapeto an oval shape. The tip of the hypodermic needle is then ground to abevel to produce a sharp point to reduce the required penetration force,as previously discussed. Finally, the top section of the needle isremoved by appropriate techniques (e.g., grinding, electropolishing,etc.). The resulting sharp 124 has a “U”-shaped configuration andprovides ample space for the insertion of sensor 14. In someembodiments, the tip-grinding step and the compression step may becarried out in reversed order.

Due to the compression step, a user may initially start with a largerdiameter hypodermic needle so that the finished sharp 124 will havesimilar dimensions to the previously described sharps.

FIGS. 11-12 illustrate the position of on body housing 122 with respectto the needle hub 136 and sharp 124. The on body housing 122 can beconfigured to hold at least a portion of sensor 14 and sensor controlunit. As illustrated in FIG. 11, the sharp 124 extends through anaperture 168 in the on body housing 122. Thus, in some embodiments, thesharp 124 is uncoupled to on body housing 122. The distal portion ofsensor 14 is positioned within the sharp 124. As further illustrated inFIG. 12, electronics of the sensor control unit (e.g., a printed circuitboard containing electronics components of the on-body unit) and sensorhub 123 are positioned within on body housing 122. Sensor 14 may includea positioning structure, or slit 127, which receives a positioningmember, such as tab 129 of sensor hub 123. A power supply 82, such as abattery, e.g., a single-use disposable battery or rechargeable battery,is provided. The power supply 82 is used to provide potential or currentto the sensor in some embodiments. In embodiments where a passivecommunications protocol such as passive RFID is used, no power supply isprovided for the communications. Such power is provided by the monitorunit. In some embodiments, where the sensor control unit is used totransmit one or more signals, one or more power supplies may be used toprovide power for such communications circuitry. In some embodiments,the active operational life of the battery may exceed the activeoperational life of the sensor 14.

FIG. 13 illustrates in cross-section the orientation of the on bodyhousing 122 with respect to the sharp 124 of an inserter, such asinserter 500 depicted in FIGS. 14-17. As discussed herein, sensor 14 isdisposed in a substantially bent configuration in some embodiments, suchthat a portion of the sensor, e.g., the insertion portion 30 and theproximal retention portion 48, are substantially vertical (i.e.,substantially aligned with the longitudinal axis of an inserter andsubstantially perpendicular to the skin surface) and the contact portion32 (shown in profile) is oriented in a substantially horizontalconfiguration, and in electrical contact with the data-processing unitelectronics, such as circuit 80. The sensor tab 50 can be encased in theplastic of the on body housing 122 (“overmolded”) and secured in place.The notch 56 provides further stability to the sensor 14, e.g., byallowing the sensor tab 50 to be encased by the material of the on bodyhousing 122, and further provides a means for vertically orienting thesensor 14 during mounting, by allowing vertical positioning of the notch56 with respect to a vertical landmark of the on body housing 122.

The sensor 14, mounted with the on body housing 122, can be disposedwithin a recess of the carriage 130 such as a concave recess in thecarriage 130. Alternatively, the sensor 14, mounted with the on bodyhousing 122, can be disposed between the support structure and one ormore projections extending from the wall of the sheath. In yet anotheralternative, the sensor 14, mounted with the on body housing 122, can beheld in position by a releasable friction fit coupling to the sharp 124.In this manner, the carriage need not have a recess within which thesensor mounted with the sensor housing is disposed. In the initialconfiguration of the inserter, the sharp 124 extends through alongitudinal aperture 168 formed in a carriage 130. In some embodiments,the aperture 168 is appropriately sized, such that neither the sharp 124nor needle hub 136 is in contact with the carriage 130. Accordingly, theneedle hub 136 (and sharp 124) on the one hand, and the carriage 130(FIG. 13) and the on body housing 122, on the other hand, movesimultaneously but independently from one another. In other embodiments,a friction fit may be provided between the aperture and the sharp.

The insertion portion 30 and proximal retention portion 48 of the sensor14 are disposed within a longitudinal bore 162 within the sharp 124(See, e.g., FIG. 6). The proximal retention portion 48 is disposedwithin the longitudinal bore of the sharp 124 and provides additionalstability to the mounting of the sensor 14 within the sharp 124. Thelongitudinal wall gap or opening 162 of sharp 124 is aligned with thesensor 14, such that the tab 50 and the contact portion 32 extendlaterally outward from the sharp 124.

An embodiment of an inserter is illustrated in FIGS. 14-17 and isdesignated inserter 500. In some embodiments, inserter 500 has a maximumdiameter of about 30 mm to about 60 mm, e.g., about 40 mm, about 43 mm,about 43.5 mm, about 50.5 mm, about 54.5 mm, etc. In some embodiments,inserter 500 has a maximum height of about 40 mm to about 80 mm, e.g.,about 44 mm, about 46 mm, about 50 mm, about 53 mm, about 67 mm, about71 mm, etc. In some embodiments, inserter 500 has a volume of about 35cm³ to about 110 cm³, e.g., about 40 cm³, about 41 cm³, about 50 cm³,about 60 cm³, about 61 cm³, about 62 cm³, about 69 cm³, about 70 cm³,about 79 cm³, about 90 cm³, about 106 cm³, etc. The maximum height ismeasured from actuator 514 to the distal surface 512 of sheath 542. Thevolume is measured as the bellows portion 502 and the portion of thesheath 542 that protrudes from bellows portion 502.

Inserter 500 includes, a bellows portion 502, a sheath 542, and aremovable distal cap 504 for maintaining a sterile environment for themedical device and sharp housed therein. As illustrated in FIG. 15,distal cap 504 is shown removed from sheath 542. Sheath 542 defines adistal surface 512 for placement on the skin of a subject. Inserter 500may be utilized to advance a medical device into the skin of thesubject. In some embodiments, bellows portion 502 is compressed in orderto advance the medical device into the skin of the subject. Bellowsportion 502 includes a series of concentric folds, including raisedportions 516 and folded portions 518.

Inserter 500 is illustrated in cross-sectional view in FIG. 16 prior touse and prior to removal of cap 504, which is attached to sheath 542 viainter-engagement of threads 510 on sheath and threads on cap 504. Cap504 includes a desiccant tablet 590. Cap 504 may further include areceptacle for maintaining the position of the sharp 524 within thesheath 542 prior to use.

As illustrated in FIG. 16, the inserter 500 includes an initialconfiguration in which the bellows portion 502 is disposed in a relaxed,extended position. In such configuration, the sharp 524 is disposed in aposition spaced apart from the aperture 520 of the adhesive layer 518.The proximal end portion of the bellows portion 502 includes a button oractuator portion 514. Extending distally from the actuator portion 514are side walls 528 and needle hub 536. Downward force on the actuatorportion 514 causes a downward force on the needle hub 536 and on thecarriage 530 (through coupling to side walls 528). Carriage 530 includesa recess 532 for reception of the on body housing 122 therein.Additionally, carriage 530 includes laterally acting spring arms thatengage detent features on the on body housing 122 periphery and allowfor easy release of on body housing 122 upon completion of insertion.Sharp 524 extends longitudinally from needle hub 536 within the inserter500. In some embodiments, the sharp is supported at an oblique angle,between about 0° and 90° with respect to the skin surface.

FIG. 17 illustrates inserter 500 in cross-section during insertion.Depression of bellows portion 502 with respect to sheath 542 against thebias of spring 546 causes distal longitudinal movement of the carriage530 and sharp 524 from a proximal position toward a distal position.During such downward, proximal movement, spring 546 is compressedbetween an upper (proximal) portion adjacent to actuator 514 and a lower(distal) portion adjacent to sheath 542. As the sharp 524 is urgeddistally, it carries the sensor insertion portion 30 of sensor 14 (FIG.12) into the subcutaneous portion of the subject's skin S. In someembodiments, a layer of adhesive between carriage 530 and sheath 542 maybe used, requiring the user to exceed a minimum force threshold to breakthe adhesive bond, thus allowing distal motion of carriage to occur.

By removing downward force on the actuator portion 514, the bias ofspring 546 provides an upward (proximal) force, which permits sharp 524to withdraw from the skin S of the subject. In some embodiments, bellows502 may provide the entire upward (proximal) force to withdraw sharp 524from the skin S.

An exemplary driver apparatus is illustrated in FIGS. 18-24 anddesignated driver apparatus 3600. It is understood that driver apparatus3600 as described herein (as well as driver apparatuses 3700, 3800,3900, and 4000) is designed for use with any inserter described herein,such as, e.g., inserter 500 (see FIGS. 14-17) or alternatively inserter2400 (see FIGS. 44-58). Moreover, in certain embodiments, driverapparatus 3600 (and 3700, 3800, 3900, and 4000) may be configured foruse with any inserter apparatus which includes an actuator button ordriver for advancing a medical device at least partially into the skinof a patient. Thus, although driver apparatus 3600 (and 3700) isillustrated in cooperation with inserter 500, it is understood that suchcombination of devices is not intended to encompass all combinations ofdriver apparatuses and inserters. Similarly, although driver apparatus3900 (and 4000) is illustrated with inserter 2400, it is understood thatsuch combination of devices is not intended to encompass allcombinations of driver apparatuses and inserters. For example, thedriver apparatuses disclosed herein provide, among other features, a“button pushing” capability in which the driver apparatus which may becoupled to the actuator button or driver of the inserter to which thedriver apparatus is attached.

Another feature of the driver apparatuses described herein ismodularity. In some embodiments, the driver apparatus and the insertermay each be capable of independent operation. For example, the insertermay include an actuator button or switch to advance the medical deviceinto the skin of the patient without use of the driver apparatus. Thedriver apparatus, to the extent provides an actuation capability, may beused with any inserter which has an actuation button that may becontacted by the driver of the driver apparatus. In some embodiments,the modularity allows the driver apparatus to be designed for multipleuses, and the inserter device is capable of a single use. In otherembodiments, the inserter is also capable of multiple uses, for example,by replacing the sensor and/or on-body housing with each use.

Driver apparatus 3600 includes a housing 3602 for positioning withrespect to an inserter. A loading element 3604—longitudinally movablewith respect to housing 3602—is provided. In some embodiments, driverapparatus 3600 is provided with an actuator, e.g., rotating cam 3606,which provides automatic actuation of an inserter. In use, arming button3620 is pressed (in direction of arrow E) to connect rack 3610 withpinion 3612 (FIG. 18). As illustrated in FIG. 18, once arming button3620 is pressed, loading element 3604 is depressed downwardly (directionof arrow D) to rotate cam 3606 in a first direction F against the biasof torsion spring 3614. Firing button 3618 maintains the spring in theloaded position until pressed.

As illustrated in FIG. 20, the driver apparatus 3600 is positioned withrespect to an inserter 500. Although inserter 500 is illustrated inFIGS. 20-24, it is understood that any inserter may be used with driverapparatus 3600. In some embodiments, the dimensions of the housing 3602and the location and shape of cam 3606 are selected to interact with thedimensions of the inserter. For example, the housing 3602 may bedesigned for snap-fit or friction-fit cooperation with the sheath 542 ofinserter 500.

As illustrated in FIG. 21, cap 504 of inserter 500 is removed (notshown), thereby allowing placement of adhesive 518 (not shown) on theskin of the subject. To insert sharp 524 (not shown), release button3618 may be depressed (arrow H).

FIGS. 22-24 illustrate the sequence of motions of the driver apparatus3600 to drive sharp 524 into the skin of the subject. As illustrated inFIG. 22, upon depressing release button 3618, torsion spring 3614 isreleased, thereby driving rotation of cam 3606 in the direction J withthe bias of the torsion spring 3614. Cam 3606 includes a surface havinga protrusion 3607. As illustrated in FIG. 23, further rotation of cam3606 causes protrusion 3607 to engage actuator button 514 of inserter500. Consequently, bellows 502 and spring 546 are compressed, and needlehub 536 and carriage 530 are advanced distally (downwardly towards theskin of the subject (Not shown in FIGS. 22-24. See, e.g., FIG. 16).Sharp 524 containing sensor 14 therein is driven into the skin of thesubject and on body housing 122 is adhered to the adhesive 518 (notshown). Further unwinding of the torsion spring causes the cam 3606 tofurther rotate, which results in protrusion 3607 being spaced from theactuator button 514, as illustrated in FIG. 24. As a result, the springbias of retraction spring 546 (not shown) returns bellows 502 to itsexpanded configuration, and retracts the sharp 524 from the skin of thesubject, leaving the sensor at least partially implanted in the skin.

Another exemplary driver apparatus for actuation of inserters isillustrated in FIGS. 25-31 and designated driver apparatus 3700. In someembodiments, driver apparatus 3700 is a reusable apparatus, whereas theinserter may be a disposable device. Driver apparatus 3700 issubstantially identical to driver apparatus 3600, with the substantialdifferences noted herein and indicated in the accompanying figures.

As illustrated in FIGS. 25 and 26, driver apparatus 3700 includes ahousing 3702 for positioning with respect to an inserter. A loadingelement 3704—longitudinally movable with respect to an upper housing3705—is provided. In some embodiments, actuator 3706 is a reciprocalelement that provides automatic actuation of an inserter. In use,loading element 3704 is advanced laterally (direction of arrow K) alonga track 3710 against the normal bias of a drive spring 3714. Uponloading of the drive spring 3714, a locking mechanism 3718 maintains theloading of spring 3714.

As illustrated in FIG. 27, the driver apparatus 3700 is positioned withrespect to an inserter 500. Although inserter 500 is illustrated inFIGS. 27-31, it is understood that any inserters may be used with driverapparatus 3700. As illustrated in FIG. 28, cap 504 of inserter 500 isremoved (not shown), thereby allowing placement of adhesive 518 (notshown) on the skin of the subject. To insert the sharp 524 (not shown),release button 3718 may be depressed (arrow L).

FIGS. 29-31 illustrate the sequence of motions of the driver apparatus3700 to drive the sharp 524 into the skin of the subject (see FIG. 16).As illustrated in FIGS. 29-31, upon depressing release button 3718,drive spring 3714 is released, thereby driving sliding member 3707 inthe direction M with the bias of the spring 3714. Sliding member 3707 isrestrained to lateral motion due its positioning in track 3710.Similarly, actuator 3706 is restrained to longitudinal motion due to itspositioning in track 3709. Sliding member 3707 is coupled to actuator3706 by a crank member 3720, which is pivotally connected to one end tosliding member 3707 and at the other end to actuator 3706. Asillustrated in FIG. 30, further lateral movement of sliding member 3707causes the actuator 3706 to advance distally and to engage the actuatorbutton 514 of inserter 500. Consequently, bellows 502 (not shown) iscompressed and needle hub 536 and carriage 530 are advanced distally,thereby driving sharp 524 into the skin of the subject and adhering onbody housing 122 (see FIG. 16) to the adhesive 518 (not shown). See,e.g., FIG. 16, for adhesive 518. Further lateral movement of slidingmember 3707 causes the actuator 3706 to advance proximally, asillustrated in FIG. 31. As a result, the spring bias of retractionspring 546 (See, e.g., FIG. 16) returns bellows 502 to its expandedconfiguration, and retracts the sharp 524 from the skin of the subject.

A driver apparatus for actuation of inserters is illustrated in FIGS.32-43 and designated driver apparatus 3800. In some embodiments, driverapparatus 3800 is a reusable apparatus, whereas the inserter may beinserter 500 described herein. Driver apparatus 3800 is substantiallyidentical to actuators 3600 and 3700, with the substantial differencesnoted herein and indicated in the accompanying figures.

As illustrated in FIGS. 32 and 33, driver apparatus 3800 includes ahousing 3802 for positioning with respect to an inserter, such asinserter 500 described herein. A loading element 3804 is provided whichis longitudinally movable with respect to housing 3802. Depression ofthe loading element causes a rotor 3808 to rotate against the bias of atorsion spring (not shown). A locking element (not shown) maintains theloading of the torsion spring.

An enhanced view of the actuation of driver apparatus 3800 is depictedin FIGS. 34-43. As depicted in FIG. 34, driver apparatus 3800 includestrigger 3810, cam 3808, arming button 3812, torsion spring 3814, shaft3816, pawl 3818, actuator 3806, and return spring 3820. To arm driverapparatus 3800, loading element 3804 (not shown) is pressed, causingarming button 3812 to be pushed down, winding shaft 3816 and thustorsion spring 3814 (FIG. 35). Pawl 3818 locks shaft 3816 into place(FIG. 36). After a user depresses loading element 3804, arming button3812 returns to its original position while shaft 3816 is held in placeby pawl 3818 (FIG. 37).

In order to actuate driver apparatus 3800, a user again pushes loadingelement 3804. This causes trigger 3810 to move in a downward motion,causing cam 3808 to be released. In some embodiments, loading element3804 is used to alternately depress arming button 3812 and trigger 3810.Cam 3808 is then driven forward by torsion spring 3814 (FIG. 38). Insome embodiments, a first loading element is used to depress armingbutton 3812, and a second loading element is used to depress trigger3810 (not shown).

As cam 3808 rotates, it pushes down on actuator 3806 (FIGS. 39-40). Atthe end of the stroke, there is a slight dwell. This allows the sensorbody to be held and pressed onto the adhesive skin patch (FIG. 41).After a full rotation, cam 3808 is stopped by trigger 3810 as shown inFIG. 43. Return spring 3820 pushes actuator 3806 back up, releasingpressure on the inserter. When trigger 3810 is released by the subject,cam 3808 continues to rotate until it is in the home position, therebyallowing driver apparatus 3800 to be used again (FIG. 43).

With continued reference to FIG. 33, inserter 500 supports an on bodyhousing 122 and sensor 14. A sharp (not shown) is used to advance thesensor into the skin of the patient. Actuator 3806 contacts actuator 114(substantially identical to actuator 514) of inserter 500 to drive thesharp and sensor downward towards the subject's skin.

An inserter 2400 in accordance with another exemplary embodiment isillustrated in FIG. 44. In some embodiments, inserter 2400 has a maximumdiameter of about 30 mm to about 60 mm, e.g., about 40 mm, about 43 mm,about 43.5 mm, about 50.5 mm, about 54.5 mm, etc. In some embodiments,inserter 2400 has a maximum height of about 40 mm to about 80 mm, e.g.,about 44 mm, about 46 mm, about 50 mm, about 53 mm, about 67 mm, about71 mm, etc. In some embodiments, inserter 2400 has a volume of about 35cm³ to about 110 cm³, e.g., about 40 cm³, about 41 cm³, about 50 cm³,about 60 cm³, about 61 cm³, about 62 cm³, about 69 cm³, about 70 cm³,about 79 cm³, about 90 cm³, about 106 cm³, etc. The maximum height ismeasured from top of housing 2402 to the bottom of housing 2402. Thevolume is measured as the volume of housing portion 2402.

With reference to FIG. 44, inserter 2400 includes a housing 2402 and aremovable distal cap 2412 for protecting the medical device and sharphoused therein. Housing 2402 and distal cap 2412 may be fabricated fromany suitable materials such as metal, plastic, etc. In some embodiments,cap 2412 may be fabricated from a polymer or plastic material.

An exploded view of the components of inserter 2400 is illustrated inFIG. 45. As shown, inserter 2400 generally comprises plunger 2405,spring 2406, housing 2402, sharp 2404, on body housing 122, sharp holder2408, adhesive patch 218, and cap 2412 when fully assembled.

A more detailed view of sharp holder 2408 is shown in FIG. 46. Needleholder 2408 retains sharp 2404 in a fixed position with respect toitself within inserter 2400, thereby allowing it to safely penetrate asubject's skin during later use.

To assemble inserter 2400, sharp 2404 is inserted through an opening inon body housing 122 as shown in FIG. 47. Needle holder 2408 preventssharp 2404 from being fully inserted through on body housing 122. Insome embodiments, on body housing 122 includes an analyte sensor 14 anda sensor control unit.

Next, plunger 2405, spring 2406, and housing 2402 are assembled as shownin FIGS. 48-50. Plunger 2405 contains a spring retention member which isinserted through the center of spring 2406. Lip 2414 of plunger 2405engages inner wall 2416 (not shown) of housing 2402 when assembled (FIG.44). This causes spring 2406 to be contained between lip 2418 of housingmember 2402 and the bottom surface 2424 (not shown) of plunger 2405. Theresulting sub-assembly of inserter 2400 allows plunger 2405 to movebetween a proximal position, with spring 2406 fully extended, and adistal position, wherein bottom surface 2424 engages wall 2426 ofhousing 2402.

The sensor housing assembly shown in FIG. 47 is then inserted into theinserter sub-assembly shown in FIGS. 48-50. As shown in FIG. 50, on bodyhousing 122 is inserted into housing 2402 with the tip of sharp 2404pointing away from plunger 2405. The resulting assembly is depicted inFIG. 51. As shown in FIG. 44, grooves on sharp holder 2408 engage tabs2422 on plunger 2405. The on body housing 122 is axially retained in thehousing 2402 by the housing arms detent features 2440 (not shown).

Finally, adhesive patch 218 is placed over the opening of housing 2402and cap 2412 is snap fit over housing 2402 as shown in FIG. 52. Thefully assembled inserter 2400 is depicted in FIG. 53. In someembodiments, adhesive pad 218 has an adhesive material on both faces. Acentral aperture 220 may be provided in adhesive pad 218 to allow sharp2404 to be deployed into the skin of a subject. During insertion, sharp2404 passes through aperture 220 and into the skin of the subjectcarrying at least the sensor with it.

FIG. 54 illustrates inserter 2400 in cross-section, in an initialconfiguration prior to use, after removal of the distal cap 2412. Asshown, sharp 2404 extends longitudinally within the inserter 2400. Insome embodiments, sharp 2404 is supported at an oblique angle, e.g.,between about 0° and 90° with respect to the skin surface.

In some embodiments, sharp 2404 is a solid needle. In some embodiments,sharp 2404 is provided with a substantially cylindrical configurationdefining an interior bore, e.g., a rigid cylindrical member or ahypodermic-style needle. Sharp 2404 may also be provided with anelongated longitudinal opening or gap in the wall. In some embodiments,sharp 2404 is fabricated from a sheet of metal and folded into asubstantially “V,” “U” or “C” configuration in cross-section to definethe longitudinal recess.

Depression of plunger 2405 causes distal longitudinal movement of onbody housing 122 and sharp 2404 from a proximal position to a distalposition. During such downward, distal movement, spring 2406 is furthercompressed between lip 2418 and bottom surface 2424. Detent 2440provides a minimum force threshold to overcome before on body housing122 can continue on its downward distal movement. Beyond a minimum forcethreshold, detent 2440 is pushed outward by on body housing 122, and onbody housing 122 then transitions onto ramp 2442. The friction betweenon body housing 122 and ramp 2442 of the housing hold the on bodyhousing 122 up against plunger 2405.

As illustrated in FIG. 55, depression of plunger 2405 advances theinserter 2400 from an initial configuration to a deployed configuration.Contact of plunger 2405 and hub 2408 during depression of plunger 2405imposes a downward force and consequential distal movement of sharp2404. As the sharp 2404 is urged distally, it carries the sensorinsertion portion 30 into the subcutaneous portion of the subject's skinS (not shown). Contact of plunger 2405 and on body housing 122 duringdepression of plunger 2405 imposes a downward force and consequentialdistal movement of on body housing 122. Lip features 2414 of plunger2405 maintain parallelism of on body housing 122 to subject skin Sduring distal movement.

When plunger 2405 reaches a distal position, as shown in FIG. 56, bottomsurface 2424 engages wall 2426 and prevents further downward movement.The distal (lower) surface of on body housing 122 engages the uppersurface of adhesive pad 218, thereby becoming adhered to the skinsurface S of the subject.

As the subject or some apparatus removes force from plunger 2405, spring2406 urges plunger 2405 toward its proximal position as shown in FIG.57, leaving on body housing 122 adhered to the skin surface S of thesubject. Tabs 2427 (not shown) provide additional force on on bodyhousing 122 to assist holding it to adhesive patch 218 while the sharp2404 is withdrawn through on body housing 122. Eventually, the upwardforce exerted by spring 2406 returns inserter 2400 to its initialconfiguration as illustrated in FIG. 58.

In some embodiments, inserter 2400 may be distributed in a sterilizedpackage 2480 as depicted in FIG. 59. To use inserter 2400 in thisconfiguration, a user would first clean the insertion site on the skinwith alcohol. The subject would then remove inserter 2400 fromsterilized package 2480 as shown in step 1. Next a subject would placethe inserter on the insertion site and push down on plunger 2405 untilon body housing 122 is adhered to the subject's skin as shown in steps2-3. The subject would then release the plunger 2405. Finally, thesubject would remove inserter 2400 from the insertion site and disposeof the inserter.

In another embodiment, the sterilized inserter 2400 shown in FIG. 59 maybe utilized with driver apparatus 3900 (FIGS. 61-79) as shown in FIG.60. In this manner, insertion of sensor housing unit is semi-automatedwhich may deliver a more consistent user experience and reduce the riskof user error. An exemplary driver apparatus is illustrated in FIGS.61-79 and designated driver apparatus 3900.

Driver apparatus 3900 includes a housing 3902 for positioning withrespect to an inserter. A release button 3904—longitudinally movablewith respect to housing 3902—is provided. The force exerted by returnspring 3906 allows release button 3904 to be moved between a proximaland distal position, as shown in FIGS. 62-65.

As illustrated in FIG. 61, the driver apparatus 3900 is positioned withrespect to an inserter 2400. Although inserter 2400 is illustrated inFIGS. 44-60, it is understood that any inserter may be used with driverapparatus 3900. Since driver apparatus 3900 and the appropriate insertermay be modular, the dimensions of the housing 3902 and the location andshape of release button 3904 are selected to interact with thedimensions of the inserter. For example, the housing 3902 may bedesigned for snap-fit or friction-fit cooperation with the sheath 2402of inserter 2400.

FIGS. 62-65 illustrate the sequence of motions of the driver apparatus3900 to drive sharp 2404 into the skin of the subject. FIG. 62illustrates driver apparatus 3900 before firing. As shown, driverapparatus 3900 comprises housing 3902, release button 3904, returnspring 3906, driver spring 3908, and plunger 3910. Three-dimensionalperspective views of housing 3902, plunger 3910, release button 3904,are depicted in FIGS. 67-69, respectively. Release button 3904 comprisestabs 3912 which engage lip 3914 on housing 3902 which prevent the upwardforce of return spring 3906 from disengaging release button 3904 andhousing 3902 (see FIG. 66). Release button 3904 also comprisesprotrusion 3918.

Plunger 3910 comprises tabs 3916 (not shown) which confine plunger 3910to housing 3902. Driver spring 3908 is disposed between the bottom ofrelease button 3904 and the top of plunger 3910. Alternatively, thedriver spring 3908 could be around the post shown of plunger 3910 andcompressed by the cylinder of button 3904.

As illustrated in FIG. 63, upon depressing release button 3904 towardshousing 3902, return spring 3906 and drive spring 3908 becomecompressed. Concurrently, protrusion 3918 causes tab 3916 to becomedisengaged from housing 3902. This allows drive spring 3908 to advanceplunger 3910 towards inserter 3900 as shown in FIG. 64. Sharp 2404 whichcontains sensor therein is driven into the skin of the subject and onbody housing 122 is adhered to adhesive pad 118.

As the subject releases pressure on the button 3904, the return spring3906 pushes it back to its initial position. As the button 3904 returns,the arms of the button pull the arms of the plunger 3910 back to itsinitial position, automatically re-engaging the tabs 3916 with thehousing 3902 (FIG. 65). The sensor remains inserted in the subject'sskin.

An exemplary driver apparatus is illustrated in FIGS. 70-79 anddesignated driver apparatus 4000.

Driver apparatus 4000 includes a housing 4004 for positioning withrespect to an inserter. An outer button 4002—longitudinally movable withrespect to housing 4004—is provided. The force exerted by a returnspring (not shown) located between housing 4004 and outer button 4002allows outer button 3904 to be moved between a proximal and distalposition, as shown in FIGS. 73-79.

As illustrated in FIG. 70, the driver apparatus 4000 is positioned ontop of inserter 2400. Although inserter 2400 is illustrated in FIGS.44-58, it is understood that any inserter may be used with driverapparatus 4000. Since driver apparatus 4000 and the appropriate insertermay be modular, the dimensions of the housing 4004 and the location andshape of cam release button 3904 are selected to interact with thedimensions of the inserter. For example, the housing 4004 may bedesigned for snap-fit or friction-fit cooperation with the sheath ofinserter 2400.

FIG. 71 illustrates an exploded view of the components of driverapparatus 4000. As shown, driver apparatus 4000 comprises outer button4002, return spring 4006, inner button 4008, housing 4004, drive spring4010, and plunger 4012. The assembled driver apparatus 4000 is shown inFIG. 72, wherein some components are partially transparent for clarity.

FIGS. 73-79 illustrate the sequence of motions of the driver apparatus4000 to drive sharp 2404 into the skin of the subject. FIG. 73illustrates driver apparatus 4000 before firing. When assembled, returnspring 4006 is encapsulated between outer button 4002 and housing 4004.Similarly, drive spring 4010 is encapsulated between the bottom of innerbutton 4008 and surface 4020 located on plunger 4012.

Outer button 4002 comprises guides 4013 which lock inner button 4008 inposition using tabs 4022. Inner button 4008 comprises rails 4015 whichallow outer button 4002 to move with respect to housing 4004.

Plunger 4012 comprises tabs 4014 which allow it to be fit into andretained within inner button 4008. Furthermore, plunger 4012 comprisesarms 4016 having appendages 4018 with openings that engage ledge 4017 onhousing 4004.

To actuate driver apparatus 4000, a subject pushes down on outer button4002 in the direction of the subject's skin causing return spring 4006and driver spring 4010 to become compressed as illustrated in FIG. 75.Eventually, tabs 4019 located on inner button 4008 cause appendages 4018to be pushed off ledge 4017 as shown in FIG. 76.

The displacement of appendages 4018 from ledge 4017 allows drive spring4010 to drive plunger 4012 towards plunger 2405 of inserter 2400 asshown in FIG. 76. Eventually, sharp 2404 is driven into the skin of thesubject and on body housing 122 is adhered to the subject as shown inFIG. 77. If there is no inserter 2400 present, the plunger eventuallystops its forward motion when the plunger arms engage ledge 4017 or whentabs 4014 engage inner button 4008.

To remove sharp 2404 from the subject's skin, the subject must removepressure from outer button 4002 which allows return spring 4006 to exertupward pressure on outer housing 4004 as shown in FIG. 78. The guides4013 pull up the inner button through rails 4015. Inner button 4008pulls up plunger 4012 by tabs 4014. The plunger 4012 is pulled up farenough to re-engage appendaqes 4018 on ledge 4017. This makes theinserter instantly ready to be re-used with no additional steps.Concurrently, the return spring located in inserter 2400 retracts sharp2404 from the subject's skin. Return spring 4006 eventually returnsdriver apparatus 4000 to its original configuration, as shown in FIG.79.

It is understood that the subject matter described herein is not limitedto particular embodiments described, as such may, of course, vary. It isalso understood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting, since the scope of the present subject matter is limited onlyby the appended claims.

What is claimed is:
 1. A medical device inserter, comprising: a bellows,a sheath, a removable distal cap defining a sterile environment with amedical device and an inserter sharp housed within the sterileenvironment, and a carriage shaped with a recess, the recess receivingan on body housing that includes sensor electronics for the medicaldevice, wherein the medical device is an analyte sensor, wherein thebellows is compressible to advance the medical device through a skinlayer, and a coil spring set within the bellows is adapted to provide aforce for withdrawing the inserter sharp after advancing the medicaldevice through the skin layer, wherein a proximal extent of the bellowsprovides an actuation portion of the medical device inserter, andfurther wherein the bellows provides the actuation portion of themedical device inserter such that a manual force applied to theactuation portion causes a compression of the coil spring set within thebellows and a downward force to be applied to the carriage.
 2. Theinserter of claim 1, wherein the removable distal cap is threaded to thesheath.
 3. The inserter of claim 1, wherein the medical device inserteris adapted so the bellows alone, provides the force for withdrawing theinserter sharp after advancing the medical device through the skinlayer.
 4. The inserter of claim 1, wherein the bellows comprises aseries of concentric folds.
 5. The inserter of claim 4, wherein thebellows comprises raised portions and folded portions.
 6. The inserterof claim 1, wherein a distal extent of the sheath provides an interfacewith the skin layer.
 7. The inserter of claim 1, wherein the analytesensor comprises a plurality of electrodes including a workingelectrode, wherein the working electrode comprises an analyte-responsiveenzyme and a mediator, wherein at least one of the analyte-responsiveenzyme and the mediator is chemically bonded to a polymer disposed onthe working electrode, and wherein at least one of theanalyte-responsive enzyme and the mediator is crosslinked with thepolymer.
 8. The inserter of claim 1, wherein the sheath includes adistal end and a proximal end.
 9. The inserter of claim 8, wherein thedistal end of the sheath is configured for placement on the skin layer,and the bellows is compressible to advance the medical device from theproximal end of the sheath to the distal end of the sheath through theskin layer.